This grant proposal is designed to test several theories regarding the action of fluoride in reducing dental caries. By carefully elucidating the mechanisms whereby fluoride reduces dental decay, we may be able to develop more effective fluoride agents or treatment regimes. A multi-disciplinary approach is being used in the work that includes chemical, morphological and histological evaluations of the reactions between various fluoride agents and sound or white spot enamel. Initial experiments have concentrated on the effects of topical fluoride agents on enamel solubility, fluoride uptake and penetration as well as caries-like lesion formation after topical treatment. Since APF at 1.23% F seems to be the topical fluoride agent most used by the clinician, our topical fluoride studies have used this agent as a positive control. We are therefore evaluating the various fluoride treatment procedures by comparison to APF. In this regard we have recently reported (IADR Abstract #284) that APF applications to sound enamel produced greater fluoride uptake than titanium tetrafluoride. On the other hand TiF4 applications afforded greater enamel solubility reductions than APF. Since these two in vitro criteria for assessing the possible anti-caries potential of preventive fluoride agents gave equivocal results, a third criteria was employed. The ability of the agents to prevent artificial lesion formation was the third criteria used. These studies showed that TiF4 was a more effective agent in preventing artificial lesion formation than APF. Thus despite the higher concentrations of fluoride in enamel after APF treatment, the surface coating produced by the TiF4 application afforded the enamel a greater degree of protection from lesion formation than APF. It would appear therefore that TiF4 may be a more effective topical fluoride agent than APF in preventing dental decay.